Craniofacial and Dental Development in the RASopathies

The RASopathies are a group of syndromes caused by mutations in genes encoding proteins in the RAS/mitogen-activated protein kinase (MAPK) signaling pathway that affect multiple organ systems. These syndromes include neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lentigines, capillary malformation–AV malformation syndrome, Legius syndrome, cardio-facio-cutaneous syndrome, and Costello syndrome. Although the RASopathies are caused by mutations in the same pathway, these syndromes have both overlapping and distinct features, including in the craniofacial complex. The craniofacial features of the RASopathies have been well delineated and are used to guide genetic testing. The oral and dental phenotypes have only more recently been characterized in greater detail and in larger cohorts. Increased knowledge of the oral and dental findings in the RASopathies has broadened our understanding of the manifestations of dysregulated RAS/MAPK signaling in the RASopathies and elucidated mechanistic roles for RAS/MAPK in craniofacial and dental development and in pathologies in the facial region. In this chapter, we review the craniofacial, oral, and dental findings for each of the RASopathies for which these phenotypes have been reported, discuss the animal models of the RASopathy syndromes that have informed our knowledge about the RAS/MAPK pathway in craniofacial and dental development, and provide oral health recommendations for dental and medical providers to consider when treating this patient population.